26831-52-7Relevant articles and documents
Discovery of seneciobipyrrolidine derivatives for the amelioration of glucose homeostasis disorders through 4E-BP1/Akt/AMPK signaling activation
Che, Jinxin,Ma, Canliang,Lu, Jialiang,Chen, Binhui,Shi, Qiuqiu,Jin, Xinxin,Song, Rui,Xu, Fan,Gan, Lishe,Li, Jingya,Hu, Yongzhou,Dong, Xiaowu
, (2021/11/16)
Modulating the glucose transport in skeletal muscle is a promising strategy for ameliorating glucose homeostasis disorders. However, the complicated mechanisms of glucose transport make it difficult to find compounds therapeutically relevant molecular mechanisms of action, while phenotypic screening is thought to be an alternative approach to mimic the cell state of interest. Here, we report (±)-seneciobipyrrolidine (1a) is first found to enhance glucose uptake in L6 myotubes through phenotype-based screening. Further SAR investigation led to the identfication of compound A27 (EC50 = 2.7 μM). Proteomiic analysis discloses the unique function mechanism of A27 through upregulating the level of the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1), subsequently enhancing the Akt and AMPK phosphorylation, thereby promoting the glucose uptake. Chronic oral administration of A27 significantly lowers blood glucose and improves glucose tolerance in db/db mice. This work is new research on seneciobipyrrolidine derivatives, providing a promising avenue for ameliorating glucose homeostasis.
Enantioselective synthesis of tunable chiral pyridine-aminophosphine ligands and their applications in asymmetric hydrogenation
Liu, Youran,Chen, Fei,He, Yan-Mei,Li, Chenghao,Fan, Qing-Hua
, p. 5099 - 5105 (2019/05/29)
A small library of tunable chiral pyridine-aminophosphine ligands were enantioselectively synthesized based on chiral 2-(pyridin-2-yl)-substituted 1,2,3,4-tetrahydroquinoline scaffolds, which were obtained in high yields and with excellent enantioselectivities via ruthenium-catalyzed asymmetric hydrogenation of 2-(pyridin-2-yl)quinolines. The protocol features a wide substrate scope and mild reaction conditions, enabling scalable synthesis. These chiral P,N ligands were successfully applied in the Ir-catalyzed asymmetric hydrogenation of benchmark olefins and challenging seven-membered cyclic imines including benzazepines and benzodiazepines. Excellent enantio- and diastereoselectivity (up to 99% ee and >20:1 dr), and/or unprecedented chemoselectivity were obtained in the asymmetric hydrogenation of 2,4-diaryl-3H-benzo[b]azepines and 2,4-diaryl-3H-benzo[b][1,4]diazepines.
Catalytic Synthesis of Indolines by Hydrogen Atom Transfer to Cobalt(III)–Carbene Radicals
Karns, Alexander S.,Goswami, Monalisa,de Bruin, Bas
supporting information, p. 5253 - 5258 (2017/12/15)
We report a new method for the synthesis of indolines from o-aminobenzylidine N-tosylhydrazones proceeding through a cobalt(III)–carbene radical intermediate. This methodology employs the use of inexpensive commercially available reagents and allows for the transformation of easily derivatized benzaldehyde-derived precursors to functionalized indoline products. This transformation takes advantage of the known propensity of radicals to undergo rapid intramolecular 1,5-hydrogen atom transfer (1,5-HAT) to form more stabilized radical intermediates. Computational investigations using density functional theory identify remarkably low barriers for 1,5-HAT and subsequent radical rebound displacement, providing support for the proposed mechanism. We explore the effect of a variety of nitrogen substituents, and highlight the importance of adequate resonance stabilization of radical intermediates to the success of the transformation. Furthermore, we evaluate the steric and electronic effects of substituents on the aniline ring. This transformation is the first reported example of the synthesis of nitrogen-containing heterocycles from cobalt(III)–carbene radical precursors.
